Light-Activated Signaling in DNA-Encoded Sender–Receiver Architectures

Abstract

Collective decision making by living cells is facilitated by exchange of diffusible signals where sender cells release a chemical signal that is interpreted by receiver cells. A variety of nonliving artificial cell models have been developed in recent years that mimic various aspects of diffusion-based intercellular communication. However, localized secretion of diffusive signals from individual protocells, which is critical for mimicking biological sender–receiver systems, has remained challenging to control precisely. Here, we engineer light-responsive, DNA-encoded sender–receiver architectures, where protein–polymer microcapsules act as cell mimics and molecular communication occurs through diffusive DNA signals. We prepare spatial distributions of sender and receiver protocells using a microfluidic trapping array and set up a signaling gradient from a single sender cell using light, which activates surrounding receivers through DNA strand displacement. Our systematic analysis reveals how the effective signal range of a single sender is determined by various factors including the density and permeability of receivers, extracellular signal degradation, signal consumption, and catalytic regeneration. In addition, we construct a three-population configuration where two sender cells are embedded in a dense array of receivers that implement Boolean logic and investigate spatial integration of nonidentical input cues. The results offer a means for studying diffusion-based sender–receiver topologies and present a strategy to achieve the congruence of reaction-diffusion and positional information in chemical communication systems that have the potential to reconstitute collective cellular patterns.

Functionalizing Lipid Sponge Droplets with DNA**

“…These reactions control uptake and release of molecular cargo that is coupled to DNA. In the future, the system could be extended to include communication between individual neighboring droplets through nucleic acid signals that could be released locally upon activation [29–31] . Communication and computations based on nucleic acids as signals can be easily programmed and multiplexed opening up new opportunities for molecular localization control and signal processing in lipid sponge droplets.…”

Functionalizing lipid sponge droplets with DNA

“…In the future, the system could be extended to include communication between individual neighboring droplets through nucleic acid signals that could be released locally upon activation. [28][29][30] Communication and computations based on nucleic acids as signals can be easily programmed and multiplexed opening up new opportunities for molecular localization control and signal processing in lipid sponge droplets.…”

Controlling Synthetic Cell-Cell Communication

“…This spatiotemporal fusion initiated expression of a fluorescent protein. Light-activated communication was also demonstrated between sender-receiver proteinosomes, using photocleavable DNA templates that could release ssDNA through semi-permeable membranes to initiate DSD reactions in neighbouring SCs ( Yang et al, 2020 ).…”